Table 1
Etiological treatment recommendations for Chagas disease in the context of COVID-19 coinfection.*
| Chagas disease status | COVID-19 status | Guidance for etiological treatment with benznidazole or nifurtimox |
|---|---|---|
| Chronic, indeterminate | Negative | Consider delaying treatment to minimize risk of COVID-19 exposure based on local epidemiological context and current physical distancing regulations. |
| Chronic, indeterminate | Positive, with or without symptoms | Consider delaying treatment until COVID-19 is completely resolved and based on local epidemiological context and current physical distancing regulations. |
| Acute cases | Negative or positive, with or without symptoms | Initiate treatment. |
| Clinical and/or parasitological evidence of reactivation | Negative or positive, with or without symptoms | Initiate treatment. |
| Chronic, indeterminate, currently undergoing etiological treatment | Positive, symptomatic | Postpone treatment; if immunosuppressive drugs are prescribed in the context of COVID-19 management, closely monitor for reactivation of T. cruzi infection by direct microscopy on peripheral blood or fluids and/or quantitative PCR (if available). If reactivation is evident, restart benznidazole/nifurtimox treatment. |
| Chronic, indeterminate, currently undergoing etiological treatment | Positive, asymptomatic | Continue treatment. |
Table 2
Potential interactions between COVID-19 treatments under investigation and CCM drugs.
| COVID-19 treatments under investigation | Potential interactions with CCM drugs |
|---|---|
| Chloroquine-hydroxychloroquine | Inhibits CYP2D6 (increasing half-life of most of the beta blockers [74] and amiodarone), and inhibits and downregulates PgP [75]. They do not interact with novel oral anticoagulants (NOACS) or vitamin K antagonists (VKAs) [76]. |
| Protease inhibitors (lopinavir-ritonavir) | By inhibiting CYP3A4, they increase plasma levels of most of CV drugs. May lower the effect of VKAs by induction of CYP2C19 and increase plasma levels of NOACs. Also may increase amiodarone levels [77]. |
| Azithromycin | Increases levels of warfarin/acenocoumarol, these anticoagulants should be withdrawn during azithromycin treatment. Due to PgP inhibition, dose reduction of NOACs may be required. |
| Atazanavir | Increases levels of VKAs and NOACs (should be discontinued). May increase amiodarone levels and effect. May increase digoxin levels. Mild increase in atenolol levels (beta blocker) [77]. |
| Remdesivir | No relevant interactions. |
| Favipiravir, Bevacizumab, Ecolizumab, Fingolimod, Pirfenidone, Interferon Methylprednisone | No relevant interactions. |
| Tocilizumab | May lower effect of anticoagulants. |
| Nitazoxanide | May increase VKA levels; do not use concomitantly. |
| Sarilumab | It is a CYP3A4 inducer, but dose modifications are not recommended. |
| Interferon and Methylprednisolone | Reduction of VKAs is advised. |
| Ribavirin | Interferes with the absorption of VKAs, possible dose increase indicated. Enalapril and other ACE2 inhibitors may provoke dry cough as well as ribavirin [78]. |
| Ivermectin | May decrease the effect of warfarin and dicoumarol. Risk of myopathy with captopril [79]. |
| Oseltamivir | No CYP interactions with CV drugs. However, case reports and series show some increase in the effect of VKAs [75]. |
| Arbidol (Umifenovir) | May decrease metabolism of labetalol (beta-blocker) [80]. |
| Canakinumab | No known drug interactions, but upregulation of CYP enzymes may further modify metabolization of CV drugs [81, 82]. |
| Anakinra | No drug interactions. |
| Emapalumab | No known drug interactions, but upregulation of CYP enzymes may further modify metabolization of CV drugs [83]. |
| Siltuximab | VKA interaction through CYP3450. Close monitoring [84]. |
| Cyclosporin A | Cyclosporin may increase digoxin levels. Amiodarone, losartan, and valsartan increase cyclosporin levels; ACE inhibitors increase nephrotoxicity [85, 86]. |
| Sirolimus | Serious warning; may increase risk of ACE inhibitor related angioedema. CYP450 and PgP interactions [87]. |
| Darunavir/cobicistat | Drugs metabolized by CYP3A4, CYP2D6, or that use the transporters PgP, BCRP, MATE1, OATP1B1 or OATP1B3 may have interactions [88]. Anticoagulants, beta blockers, and digoxin should be used with caution. |
Table 3
Understanding the interactions between COVID-19 and CD: Gaps and needs.
| Disease interaction | Clinical questions | Drug development needs |
|---|---|---|
|
|
|
Table 4
Potential impact of COVID-19 on CD healthcare roadblocks.
| Area | Potential impact of SARS-CoV-2 on key roadblocks |
|---|---|
| Prevention |
|
| Diagnosis |
|
| Etiological treatment |
|
| Diagnosis and treatment of clinical complications |
|
| Psychosocial |
|